Transferrin improved the generation of cardiomyocyte from human pluripotent stem cells for myocardial infarction repair

Human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) hold great promise for the repair of the injured heart, but optimal cell production in a fully chemically defined and cost-effective system is essential for the efficacy and safety of cell transplantation therapies. In this study, we provided a simple and efficient strategy for cardiac differentiation from hPSCs and performed functional evaluation in a rat model of myocardial infarction. Using a chemically defined medium including four components, recombinant human albumin, ascorbic acid, human transferrin, and RPMI 1640, we developed a manageable and cost-effective protocol for robust generation of CMs from hPSCs. Interestingly, the addition of transferrin helped hPSCs to transit from TeSR-E8 medium to the simple cardiac differentiation medium and successfully initiated mesoderm differentiation without significant cell death. The CM generation efficiency was up to 85% based on cTnT expression. We performed transcriptome profiling from differentiation day 0 to 35, and characterized interesting dynamic change of cardiac genes. CMs derived from transferrin-supplemented simple medium have similar transcriptome and the maturation level compared to those generated in B27 minus insulin medium as well as their in vivo counterparts. Importantly, after transplantation, hPSC-derived CMs survived in the infarcted rat heart, significantly improved the physiological function and reduced fibrosis. Our study offers an easy-to-use and cost-effective method for cardiac differentiation and facilitates the translational application of hPSC-derived CMs for heart repair.

Automated summary

This study presented a simple and efficient strategy for cardiac differentiation from human pluripotent stem cells (hPSCs) and conducted functional evaluation in a rat model of myocardial infarction. The addition of transferrin facilitated the transition of hPSCs from TeSR-E8 medium to a simple cardiac differentiation medium, leading to successful initiation of mesoderm differentiation without significant cell death. The generated cardiomyocytes (CMs) showed similar transcriptome and maturation levels to those produced in a traditional medium, and significantly improved physiological function and reduced fibrosis in the infarcted rat heart after transplantation.